Protein binding of acidic drugs

Generally, plasma protein binding of acidic drugs (e.g., warfarin, pheny-toin) is decreased in CKD, whereas binding of basic drugs (e.g., quinidine, lidocaine) is usually normal or slightly decreased or increased. 

Patients with renal disease often have hypoalbuminaemia, which reduces the protein binding of acidic drugs, such as phenytoin, thiopentone or paracetamol, with an enhanced pharmacological effect. 

The protein binding of basic drugs tends to be normal or only slightly reduced (25). In some cases, this may reflect the facts that these drugs bind to oti-acid glycoprotein and that concentrations of this glycoprotein are higher in hemodialysis-dependent patients than in patients with normal renal function. 

Dahms M, Spahn-Langguth H (1996) Covalent binding of acidic drugs via reactive intermediates detection of benoxaprofen and flunoxaprofen protein adducts in biological material. Pharmazie 51 874-881... 

Distribution - Valproic acid is rapidly distributed. Volume of distribution of total or free valproic acid is 11 or 92 L/1.73 m, respectively. Valproic acid has been detected in CSF (approximately 10% of total concentrations) and milk (about 1% to 10% of serum concentrations). Therapeutic range is commonly considered to be 50 to 100 mcg/mL of total valproate. The plasma protein binding of valproate is concentration-dependent. Protein binding of valproate is reduced in the elderly, in patients with chronic hepatic diseases, in patients with renal impairment, and in the presence of other drugs (eg, aspirin). Conversely, valproate may displace certain protein-bound drugs (eg, phenytoin, carbamazepine, warfarin, tolbutamide). 

Some disease states (e.g., hyperalbuminemia, hy-poalbuminemia, uremia, hyperbilirubinemia) have been associated with changes in plasma protein binding of drugs. For example, in uremic patients the plasma protein binding of certain acidic drugs (e.g., penicillin, sulfonamides, salicylates, and barbiturates) is reduced. 

Since milk is more acidic (pH 6.5) than plasma, basic compounds (e.g., alkaloids, such as morphine and codeine) may be somewhat more concentrated in this fluid. In contrast, the levels of weak organic acids will probably be lower than those in plasma. In general, a high maternal plasma protein binding of drug will be associ-... 

A number of proteins are commercially available as CSPs including a-acid glycoproteins (AGP, the major plasma binding protein for basic drugs), human serum albumin (HSA, the major plasma binding protein for weakly acidic drugs), bovine serum albumin (BSA), ovomucoid (OVM), and cellobiohydro-lase (CBH) [12]. The proteins are bonded to silica and utilized in reversed-phase mode with an aqueous buffer/organic modifier eluent. Mobile-phase... 

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